Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents

  • J Nat Prod. 2008 Mar;71(3):313-20. doi: 10.1021/np070377j.
Rogelio Siles  1 ,  J Freeland Ackley ,  Mallinath B Hadimani ,  John J Hall ,  Benon E Mugabe ,  Rajsekhar Guddneppanavar ,  Keith A Monk ,  Jean-Charles Chapuis ,  George R Pettit ,  David J Chaplin ,  Klaus Edvardsen ,  Mary Lynn Trawick ,  Charles M Garner ,  Kevin G Pinney
Affiliations
  • 1. Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798-7348, USA.
PMID: 18303849 DOI: 10.1021/np070377j
Abstract

Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2',3'-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected human Cancer cell lines in vitro (average GI 50 = 13.9 nM) and also showed good activity in regard to inhibition of tubulin assembly (IC 50 = 2.8 microM). In addition, a single dose (10 mg/kg) of compound 17 caused a 40% tumor-selective blood flow shutdown in tumor-bearing SCID mice at 24 h, thus suggesting the potential value of this compound and its corresponding salt formulations as new vascular-disrupting agents.